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Autoimmune disease: Could modified red blood cells lead to new treatments?

New treatments that prevent and alleviate autoimmune diseases may come from using red blood cells to carry disease-specific proteins that retrain the immune system. So concludes a study that shows such an approach works in mice with multiple sclerosis and type 1 diabetes.

The researchers say that their method of using red blood cells to carry antigenic peptides could be an effective way to induce immune tolerance and alleviate symptoms of autoimmune diseases.

The study - led by the Whitehead Institute for Biomedical Research in Cambridge, MA - is about to be published in PNAS.

An autoimmune disease is one in which the immune system mistakenly attacks the body's own cells, tissues, and organs.

While the exact causes of many autoimmune diseases remain largely unknown, experts tend to agree that genes - together with infections and other environmental factors - play an important role.

A recent review of published evidence finds that global rates of autoimmune diseases have increased considerably over the past 30 years, particularly in industrialized nations.

Estimates from the National Institutes of Health (NIH) suggest that there are more than 23 million people in the United States living with autoimmune diseases.

No cures have yet been discovered for autoimmune diseases, although treatments that manage or alleviate the symptoms are available for many of them.

Applying the principle of 'tolerance induction'

Many treatments involve giving patients drugs that suppress the immune system so that it does not overreact. However, such a blanket approach means that the immune system is not strong enough to tackle other illnesses.

Researchers are therefore looking for ways to intervene only in that part of the immune system that is mistakenly reacting in the particular disease.

For the new study, the team sought to improve a technique called "tolerance induction," which sounds good in theory but is proving difficult to apply.

The principle of tolerance induction is to use antigenic peptides or protein fragments from the particular cells that the immune system is overreacting to and retrain the immune system to ignore them.

However, scientists are finding the idea difficult to put into practice. For example, a particular stumbling block is getting the antigenic peptides to reach their destination before immune cells break them down.

To work around this, the team behind the new study decided to try a method that uses red blood cells to carry the antigenic peptides.

The team says that red blood cells are particularly well-suited to carrying the disease-specific antigen because they can reach almost every part of the body; they bring life-giving oxygen to cells.

Another reason is that red blood cells are recycled frequently - every month in mice and every 4 months in humans - without eliciting an immune system response.

Mechanism not well understood

For the new study, the researchers built on previous work in which they had attached a chemical tag and antibodies to red blood cells using a method that they called "sortagging."

They used sortagging to attach antigens that trigger the disease-specific immune response to red blood cells from mice with MS and type 1 diabetes, and then transfused them back into the mice. The whole procedure took around 1 hour.

The results showed that the mice had reduced symptoms of the disease and even one transfusion before the disease developed was sufficient to lessen symptoms, note the researchers.

"Essentially what we're doing," explains first author Novalia Pishesha, a graduate student who carried out some of the work at the Whitehead Institute, "is hijacking the red blood cell clearance pathway, such that the foreign antigen masquerades as the red blood cells' own, such that these antigens are being tolerated in the process."

However, the researchers caution that while their results suggest that using red blood cells to carry antigenic peptides appears to be an effective way to induce immune tolerance, the underlying molecular and cellular mechanisms are not clear.

They suggest that their study offers a good starting point for further research into how the immune system regulates itself and why it sometimes does the wrong thing.

Nevertheless, co-senior author Harvey Lodish, a Whitehead founding member and professor of biology, says that: "This is a very promising step in the development of therapies for autoimmune diseases," and concludes:

"If this type of response is also true in humans, then it could make a lot of these therapies possible for these diseases and similar conditions."

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